Vol. 284, Issue 3, 1227-1233, March 1998

Corticosteroids Alter 5-Hydroxytryptamine_1A Receptor-effector Pathway in Hippocampal Subfield CA3 Pyramidal Cells¹

Dayne Y. Okuhara and Sheryl G. Beck

Department of Pharmacology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois

Corticosteroids influence neuron activity in the hippocampus through the activation of mineralocorticoid and glucocorticoid receptors. For example, corticosteroids modulate the responses elicited by the activation of several different neurotransmitter receptors on hippocampal pyramidal cells. However, the effects of corticosteroids on the serotonin (5-HT) receptors systems in subfield CA3 are not completely known. Therefore, we used single-electrode voltage clamp techniques to examine the actions of chronic corticosteroid treatment on the 5-HT_1A receptor-effector pathway in rat hippocampal subfield CA3 pyramidal cells. Activation of the 5-HT_1A receptor increases the conductance of an inward rectifying potassium channel, increasing outward current. The treatment groups used in this investigation were: adrenalectomy, selective mineralcorticoid receptor activation with aldosterone, mineralcorticoid receptor and glucocorticoid receptor activation with high levels of corticosterone and SHAM. Corticosteroids altered the characteristics of the 5-HT concentration-response curve for the 5-HT_1A receptor. The effective concentration at 50% of maximum value was smaller in cells from the adrenalectomy treatment group compared to the other treatment groups. The maximum response was smaller in cells from the high corticosterone treatment group compared to SHAM and adrenalectomy treatment group animals. G protein function was also altered by corticosterone treatment. Less current was elicited by guanosine 5-0-13-thiotriphosphate in cells from the high corticosterone treatment group compared to the other treatment groups and in cells from the SHAM treatment group compared to adrenalectomy treatment group animals. Corticosteroid treatment did not alter the current-voltage relationship, the conductance or the reversal potential of the potassium current linked to the 5-HT_1A receptor. We conclude that corticosteroids alter the 5-HT_1A receptor-mediated-response in hippocampal subfield CA3 neurons at site(s) downstream of the receptor.